Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjögren's Syndrome

Xu, Junji; Su, Yingying; Hu, Lei; Cain, Alexander; Gu, Yun; Liu, Bowen; Wang, Songlin; Wang, Hao

doi:10.1089/scd.2017.0161

Cited by 16 publications

(16 citation statements)

References 37 publications

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“…Confirming these observations, the overexpression of BMP6 in the SGs of genetic modified C57BL/6 mice results in a SS-like phenotype [ 126 ], although the underlying mechanism is not clear. Xu et al assumed that BMP6 could indirectly determine immune cell infiltration of SGs through the impairment of mesenchymal stem cell function [ 127 ]. Other studies suggested that BMP6-induced SG dysfunction was rather associated with an altered glandular cell water permeability or ECM protein modulation [ 125 , 126 , 128 ].…”

Section: Future Perspectives On Alternative Molecular Mechanisms Mmentioning

confidence: 99%

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

Sisto

Ribatti

Lisi

2021

IJMS

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There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

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Section: Future Perspectives On Alternative Molecular Mechanisms Mmentioning

confidence: 99%

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

Sisto

Ribatti

Lisi

2021

IJMS

View full text Add to dashboard Cite

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“…Although the overexpression of BMP6 creates SS-like phenotypes in animal models, the underlying mechanism is not clear [143]. Xu et al assumed that BMP6 may indirectly induce immune cell infiltration via mesenchymal stem cell function impairment [145]. Other studies suggested that BMP6-induced salivary gland dysfunction had a weak link with immune cell regulation and was rather associated with the loss of glandular cell water permeability or ECM modulation [142][143][144].…”

Section: Sjögren's Syndromementioning

confidence: 99%

TGF-β Pathway in Salivary Gland Fibrosis

Zhang

Yun

Han

et al. 2020

IJMS

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Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren’s syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

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“…Anti-BMP6 targeted therapy increased the production of prostaglandin E2 (PGE2), but had no effect on other soluble factors (indoleamine 2,3-dioxygenase [IDO], nitric oxide [NO], transforming growth factor [TGF]-β). As Figure 3 shows, anti-BMP6 treatment induced an increase in PGE2 and a decrease in interferon (IFN) gamma and interleukin (IL)-17 via DNA-binding protein inhibitor (Id)1 [ 12 , 13 ]. BMP6 altered the immunomodulatory properties of SGMSCs by inhibition of proteins involved in Id1 [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

Treatment of Sjögren’s Syndrome with Mesenchymal Stem Cells: A Systematic Review

Chihaby

Orliaguet

Demoersman

et al. 2021

IJMS

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Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy. Some studies have explored the use of MSCs to treat Sjögren’s syndrome (SS), a chronic inflammatory autoimmune disease that mainly affects exocrine glands, including salivary and lacrimal glands, although current treatments are only palliative. This systematic review summarizes the current data about the application of MSCs in SS. Reports show improvements in salivary secretions and a decrease in lymphocytic infiltration in salivary glands in patients and mice with SS after intravenous or infra-peritoneal injections of MSCs. MSC injections led to a decrease in inflammatory cytokines and an increase in anti-inflammatory cytokines. However, the intrinsic mechanism of action of these MSCs currently remains unknown.

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Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjögren's Syndrome

Cited by 16 publications

References 37 publications

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

TGF-β Pathway in Salivary Gland Fibrosis

Treatment of Sjögren’s Syndrome with Mesenchymal Stem Cells: A Systematic Review

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